Hepatitis Scotland e-Bulletin April 2014

Money Changes Everything

- describe the impact of Welfare Reform on users of drug services- showcase service responses to Welfare Reform- outline the range of agencies who may be involved in improving responses to Welfare Reform- be a networking opportunity for people to discuss possible joint work in this area

Access booking from and draft conference programme at the SDF website.

This conference takes place after a recent Joseph Rowntree Foundation report which shows poverty and poor health are strongly linked.

World Hepatitis Day Campaign Pack launched

This campaign pack is intended to support health boards and organisations who may wish to run activities or events around or on World Hepatitis Day on July 28th, which in turn will support the national advertising campaign. The campaign is due to start on the the 7th of July and will once again see Big Red Cs on display in cities across Scotland and bus and train advertisements in various healthboard areas with the slogans 'Ever injected? Get tested' and 'See it, treat it, beat it - Hep C. It can be cured'.

You can find the campaign pack on the Hepatitis Scotland website and it will shortly be available on the campaign website www.hepcscot.org.

Low dose oral interferon to prevent relapse

In a Taiwanese study, patients with mild ﬁbrosis who had received low-dose (500 IU) oral HBL interferon-alpha had a lower relapse rate compared to a control and high dose group. In another finding in thrombocytopenic patients, low-dose interferon s expedited platelet count recovery. The authors suggested that there may be an immune modulating pathway mediated by low dose oral interferon through mucosa route and that this effect is independent of the antiviral effect of high dose pegylated interferon.

Schizophrenia not a problem in Hepatitis C treatment

Research recently conducted in Glasgow sought to establish the safety and efficacy of Hepatitis C treatment for patients with schizophrenia. The study highlighted that although treating chronic hepatitis C with pegylated interferon alpha may induce or exacerbate psychiatric illness, patients with schizophrenia are good candidates for hepatitis C treatment, with equivalent SVR and treatment discontinuation rates to patients without schizophrenia.

Outcomes on SVR, treatment termination and adverse events were compared. The research found that people with schizophrenia had better SVR rates than those who didn’t and adverse events leading to treatment cessation were comparable to non schizophrenic patients. None of the schizophrenic patients had to stop treatment due to psychiatric events. Reasons postulated for this include better treatment compliance among schizophrenic patients, good compliance with psychiatric medication and being psychiatrically stable prior to commencement of treatment.

Further Hep C treatment progress

Janssen’s Simeprevir granted marketing licence in Europe

Simeprevir (Olysio) has received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) recommending it be granted a marketing licence in the EU.

Merck announces strong results in HIV/HCV co-infection trial

Merck has released the results of their phase 2 trial of it’s MK-5172/MK-8742 treatment for Hepatitis C and HIV co-infection. The treatment is a once a day oral regimen which combines protease inhibitor MK-5172 and NS5A inhibitor MK-8742. The 12 week study resulted in strong HCV suppression and was proven to be safe among genotype 1 infected patients.

At 12 weeks all 29 patients who received the combination pill along with ribavirin and 26 out of 29 who received only the combination pill had HCV RNA levels of less than 25 IU/ml. The control group of 13 people with only Hepatitis C infection also achieved these levels of viral suppression.

Bristol Myers Squibb report high cure rates for triple combo pill

BMS 12 week, triple combination, all oral therapy of NS5a inhibitor daclatasvir, protease inhibitor asunaprevir and non-nucleoside BMS-791325 has reported up to 92% cure rates in a recent patient trial, noting no difference in outcomes for cirrhotic patients versus non cirrhotic patients. The treatment regimen was well tolerated with only 2 of 166 having to discontinue treatment due to adverse effects.

Phase 2a trial for Hep B 'functional cure'

Arrowhead has completed enrolment and begun dosing 8 patients in the first cohort of their phase 2a clinical trial of ARC-520, an RNAi therapeutic for the treatment of chronic Hepatitis B. The trial will eventually enrol 16 patients.The goal of this trial will be to evaluate ‘the depth and duration of Hepatitis B surface antigen decline, among other measures in response to a single dose of ARC-520’.

The company expects dosing to be completed by the 2nd quarter of 2014 with top line results being released in quarter 3.

Until recently DNA vaccine trials in larger animals hadn’t been particularly successful compared with trials in mice, but the researchers have developed a technique which makes them much more effective in large animals, stimulating the body’s immune response and helping to deliver the vaccine.

This technique involves injecting the vaccine into the skin rather than into the muscles because skin has a greater proportion of white blood cells, which are important for developing immunity to these viruses.

"What we need to do is to target that small population of white blood cells, which circulate generally in the body, and unless the vaccine targets those cells, the vaccine isn't effective and isn't efficient in any way..... So we've developed a strategy that targets these white blood cells in an indirect manner; we generate a little inflammation and that attracts all these white blood cells to that site of vaccination....We kill the cells that the vaccine is targeted to, and then those dead cells are highly inflammatory and they attract more of these white blood cells, so that is the difference," Professor Gowans said.

New Hepatitis C drugs must be made accessible more quickly than HIV drugs were

In this Guardian Poverty Matters blog , Philippe Douste-Blazy, former French Foreign Minister and current chair of Unitaid says that new treatments for Hepatitis C must be made accessible faster than HIV drugs were, especially to the world’s poorest in order to effectively tackle the global epidemic.

Gilead has priced their new drug Sovaldi (sofosbuvir) at $84,000 per 3 month treatment course and there are concerns that this drug and others will be priced out of the reach of those who need it most. He points out that drug companies are likely to offer the poorest countries less expensive versions of their drugs, but cites an article in the Lancet Journal according to which middle income countries considered to be emerging markets are unlikely to receive discounts, with 75% of the global Hepatitis C population living in these countries.

Concerns on patient access to new Hepatitis C treatments has seen a diverse group of countries including Brazil, Columbia, Costa Rica, Egypt, Moldova and South Africa to sponsor a resolution at the World Health Organisation urging the international community to act quickly on hepatitis.

Charles Gore, President of the World Hepatitis Alliance, also used Scotland’s Hepatitis C patient conference on March 19th to call for increased patient activism and pressure on MP’s and MSP’s to keep the issue of Hepatitis C and access to treatment on the agenda, with some patients expressing concerns on the accessing of new treatments in Scotland.

Gilead offers Egypt 99% discount on sofosbuvir

In response to some of the concerns raised by health campaigners and governments over accessibility to new Hepatitis C drugs, Gilead Sciences has agreed a deal with the Egyptian government to sell Sofosbuvir to them at a 99% discount on the US price, meaning a 3 month course of treatment would cost $900 rather than $84,000. Egypt currently has the highest prevalence of Hepatitis C in the world.

Gregg Alton, Head of Corporate and Medical Affairs at Gilead, said,’ We believe Sovaldi (sofosbuvir) could have a major impact on public health in Egypt by significantly increasing the number of people who can be cured of hepatitis C’.

Following a recent challenge to their patent for sofosbuvir in India, the company have also said that it will license the drug to a number of Indian generic manufacturers which would then be able to sell lower priced copies of it.

Research has been published providing the first evidence that peg interferon alfa/ribavirin dual therapy for those co-infected with Hepatitis B and Hepatitis C improved survival rates, although did report an increase in incidence of mood disorders and thyroid problems.

Before now it had not been known whether dual therapy was effective in reducing mortality or rates of hepatocellular carcinoma in this patient group.

Hep B patients with treatment response still at higher risk compared with patients who have inactive virus

The study involved over 2,300 Hepatitis B patients and showed that 7.7% of those who were started on Hepatitis B antiviral therapy had developed HCC within 42 months compared with just 1.1% of those with inactive HBV virus.

The use of Hepatitis B antivirals can effectively suppress the replication of the Hepatitis B virus, inducing a state similar to inactive Hepatitis B infection. However, the study showed those who have active viral infection and are receiving and responding to treatment are still at a higher risk of liver cancer.

The silence of the genes

Australian company Benitec Biopharma are developing what they are calling a ground breaking ‘single dose cure’ for Hepatitis C using gene silencing. It targets 3 separate, well conserved regions of Hepatitis C at the same time and also stops generation of drug resistant mutants. The 3 targeted parts of the Hep C genome are present across all genotypes so TT-034 could be applied to all HCV conditions.

An application for a clinical trial to the US FDA has been successful and will go ahead this year with 14 patients being treated with the gene silencing technology.

Australian vaccine breakthrough

Researchers from Adelaide claim they have made a breakthrough in tackling HIV and Hepatitis C with a new type of DNA vaccine which protects against the viruses and could possibly lead to a cure. Professor Eric Gowans of the University of Adelaide says that the vaccine had already shown positive results in animal trials and that human trials are due to begin in 2015.

Until recently DNA vaccine trials in larger animals hadn’t been particularly successful compared with trials in mice, but the researchers have developed a technique which makes them much more effective in large animals, stimulating the body’s immune response and helping to deliver the vaccine.

This technique involves injecting the vaccine into the skin rather than into the muscles because skin has a greater proportion of white blood cells, which are important for developing immunity to these viruses.

"What we need to do is to target that small population of white blood cells, which circulate generally in the body, and unless the vaccine targets those cells, the vaccine isn't effective and isn't efficient in any way..... So we've developed a strategy that targets these white blood cells in an indirect manner; we generate a little inflammation and that attracts all these white blood cells to that site of vaccination....We kill the cells that the vaccine is targeted to, and then those dead cells are highly inflammatory and they attract more of these white blood cells, so that is the difference," Professor Gowans said.

Staying with Australia....

The government in New South Wales, Australia, has created a new interactive online party experience aimed at 18-24 years to educate them about the risks of contracting Hepatitis C. This was in response to concerns that young people had misconceptions around Hepatitis C and based on where young people who are not injecting drug users might encounter the greatest risk of Hepatitis C.

Sexual risk and sharing risk: it's not the same!

A qualitative life history study published in the journal Drug and Alcohol Dependence has concluded that Hepatitis C prevention messages which add on safe sex information may do more harm than good.

It recruited people who had been injecting drugs for over 6 years and looked at their social practises and Hepatitis C avoidance strategies. A majority of those in relationships reported that they shared needle and syringes with their primary sexual partner (discriminate sharing). Participants commonly rationalised this in terms of 'risk equilavence' with sexual practises.

Participants reported having unprotected sex with their primary sexual partner and believed that Hepatitis C could be easily transmitted through sex. Believing that sexual risk was the same as risk from sharing injecting paraphenalia, they were willing to share injecting paraphenalia with their partner, reasoning that they probably had Hepatitis C anyway.

The majority of participants reported infrequent condom use with sexual partners, with unprotected sex with long term partners the norm. Discriminate sharing of injection equipment was reported by 62% of participants. Of those, 70% described primarily sharing with sexual partners with the other 30% reporting only ever having shared with a past or present sexual partner.

Perceptions of sexual and injecting risk were often associated with notions of trust and fidelity, with sexual fidelity linked to perceptions of injecting safety. For some, trust in a partner was framed in regard to assumed sexual fidelity which extended to trust of injecting fidelity. So in these contexts of trust, a risk equivalence narrative was being employed to position discriminate sharing as relatively safe. However, it was found that in some cases the risk equivalence narrative was maintained even when trust was eroded, with fatalism on risk meaning continual unsafe sex and risk equivalence on sharing injecting equipment.

In contrast to these perceptions, although HCV transmission by sexual activity remains low in long-term monogamous HCV heterosexual couples, strict recommendations should still be made regarding sexual practices, that is, protected anal intercourse and protected vaginal intercourse during menstruations.

HIV, Hepatitis B virus co-infection and Hep D

The prevalence of Hepatitis D infection among those co-infected with Hepatitis B and HIV has increased markedly since 1992 according to recent study findings. Additionally Hepatitis D was associated with Hepatitis flares and syphilis.

Meanwhile a study by Spanish researchers published in Clinical Infectious diseases has found that co-infection with Hepatitis D is a major risk factor for hepatic decompensation and liver related death in people living with HIV. Over an average of 80 months of follow up, Hepatitis D infection was found to be the biggest risk factor for serious liver disease and death.

Gay men willing to consider risk reduction after Hep C diagnosis

A qualitative study of HIV positive gay men in France has shown they need more information about the sexual transmission of Hepatitis C. The moment of Hepatitis C diagnosis, during a period of emotional turmoil seemed to present a limited opportunity for men to absorb information and reconsider their sexual practises.

The respondents either occasionally, regularly or consistently had unprotected anal sex with casual partners and many practised HIV serosorting when looking for sexual partners in order to have unprotected sex.

While some respondents had been aware of the possibility of sexual transmission of Hepatitis C before their own diagnosis (often because they knew someone with it) most said they did not have clear information on transmission routes.

Whilst sexual transmission of Hepatitis C is rare among heterosexuals, men who have sex with men (particularly HIV positive men) are at increased risk due to specific sexual practises.

UK experience in treating children with Hepatitis C

A recent study has reviewed the efficacy and tolerability of peg interferon alfa and ribavirin in children. They found that children respond well to dual therapy treatment with minimal impact on quality of life and no significant effect on growth. The study also said that knowledge of viral and IL28 genotypes and early viral response were useful in planning treatment and providing appropriate counselling.

US Hep B vaccination and testing low in primary care where sexual exposure is a risk

A recent Californian study published in the Clinical Journal of Infectious Diseases has found that few adults at risk of Hepatitis B because of diagnosis with an STI (sexually transmitted infection) are being tested for exposure and even fewer still are initiating vaccination.

Identifying HI-gher risks for co-infection

HIV and Hepatitis C transmission networks are strongly linked according to research published in the International Journal of Epidemiology.

It combined clinical data with phylogenetic analysis of HIV samples from a drug resistance database finding that the likelihood of HCV infection was increased by a factor of 2 if a patient was clustered with another patient with HCV.

The study authors said, “Our results indicate that the transmission networks of HIV and HCV are correlated and overlap even beyond the degree that can be expected by demographic variables such as risk group…geography, sex and age.....Thus, our analysis shows that the location of an HIV-infected patient on the HIV phylogeny can serve as an indicator for the risk of an HCV coinfection.”

This has particular implications for MSM, a group with increasing rates of incident HCV infection in HIV positive MSM. The study authors note the fact that those infections occur preferentially in MSM due to high risk sexual behaviour, the association of HCV with other sexually transmitted infections (STIs) and the recent decrease in condom use, suggesting that the rise of HCV in MSM may be due to increased risk taking in this group - making it crucial to understand the interaction between HIV and HCV in order to be able to identify high risk populations fot he spread of Hepatitis C beyond obvious groups such as IDU.

They say that the direct interpretation of their finding that HCV cases cluster on the HIV phylogeny, explains the clustering by the fact that HIV and HCV directly share transmission routes. A clustering of two pateints on the HIV phylogeny implies a proximity on the contact network and hence also on the contact network on which HCV can spread. Thus 2 individuals who cluster on the HIV phylogeny are also more likely to belong to the same HCV transmission chain.

The researchers conclude that patients whose HIV virus is closely related to the HIV virus of HIV/HCV co-infected patients have a higher risk for either being Hep C positive or becoming infected themselves. They say this indicates the occurence of domestic and sexual transmission of Hepatitis C and allows the identification of patients with a high Hepatitis C virus risk, which could help inform interventions.

Starting HIV therapy reduces risk of liver disease in HCV co-infected

Starting HIV antiviral therapy has been found to significantly reduce the risk of serious liver disease in patients co-infected with Hepatitis C according to results of a large US study. It reduced the risk of decompensated cirrhosis between 28 and 41% on average.

The researchers said that their findings provide direct evidence for consideration of antiretroviral therapy in HIV/HCV co-infeced patients regardless of CD4 count.

MPs say more must be done to tackle liver disease

MPs have said government must address the ‘catastrophic consequences’ of ignoring the burden of liver disease in an all party Westminster parliamentary hepatology group report.

Recommendations in the report include a minimum 50p per unit alcohol price, the co-ordination of a national approach to preventing liver disease including better prevention, care and diagnosis; as well as action on obesity and eliminating Hepatitis C within the next 15 years. An estimated 216,000 people in the UK are infected with Hepatitis C.

Charles Gore of the Hepatitis C Trust highlightedthe fact that only 3% of Hepatitis C patients receive potentially lifesaving treatment at the moment when new treatments could eliminate the virus within a generation. Andrew Langford of the British Liver Trust said liver disease in the UK was a ‘national scandal’ and that much more had to be done.